This project involves my work with lupus and other autoimmune diseases. The role of genetic susceptibility in lupus has been extensively examined, but the idea that lupus can be explained solely by genetics is not supported by recent studies. The concordance rate among monozygotic twins is currently thought to be 25% - 33%, substantially lower than the 75% figure derived from small studies subject to substantial selection bias published in the 1960s and 1970s. There is a clear need to look beyond genetics in order to understand this and other autoimmune diseases. My work represents a broader approach to studying lupus. It is an approach that is based on the often-cited idea that lupus involves a combination of, and interaction between, genetic and environmental factors. This work focuses on genetic factors and on measures of endogenous hormonal exposures, exogenous sources of estrogen, and on environmental exposures that may affect the risk of lupus and of other autoimmune diseases. Importantly, I have used sound methodologic designs to develop the studies within this research program, including population-based approaches to identifying patients and appropriate comparison groups. I have also developed innovative approaches to exposure assessment within the context of case-control studies. The specific studies that have been completed or are currently underway within this project include: 1) The Carolina Lupus Study - the first large, population-based case-control study of genetic, hormonal, and environmental risk factors for lupus in the US 2) Dietary Risk Factors for Lupus - a prospective analysis using data from the Nurses' Health Study (I and II) 3) Parity and Risk of Systemic Sclerosis - an analysis using a unique resource, the hospitalization and pregnancy registries covering the entire population of Sweden 4) Pesticide Exposure and Risk of Rheumatoid Arthritis - an analysis using the Agricultural Health Study cohort of spouses of licensed pesticide applicators 5) Antinuclear Antibodies and Other Markers of Immune Function - an analysis using the controls in the Carolina Lupus Study to determine the prevalence of antinuclear antibodies in the general population, and the relation between specific demographic and environmental exposures with high-titer levels of antinuclear antibodies in the absence of diagnosed disease. This project also includes an analysis of serum DDE levels in relation to immunoglobulin and autoantibodies among African-American farmers 6) The Early Disease Course of Systemic Lupus Erythematosus - an analysis of mortality, quality of life, health care utilization, and employment status in the first 4 years post-diagnosis of lupus 7) Silica Exposure and Small Vessel Vasculitis - an analysis of occupational exposures in 129 ANCA-glomerulonephritis patients diagnosed between 1997 and 2003 in North Carolina, South Carolina, Georgia and southern Virginia and 109 population-based controls